A Single Arm, Phase II Study of the Anti-Blys Monoclonal Antibody, Belimumab in Symptomatic Waldenstroms Macroglobulinaemia
- At least 18 years of age.
- Diagnosis of WM histologically confirmed on bone marrow biopsy.
- Detectable IgM paraprotein >5 g/L
- Less than 3 lines of prior therapy for WM
- Full blood count within 4 weeks prior to screening shows ANC >1.0 x109/l AND platelet
count >50 x109/l
- Therapy indicated due to development of one or more of the following:
1. symptomatic anaemia
2. hyperviscosity symptoms
3. rapidly rising paraprotein of >25% or >5g/l over 3 months
5. bulky lymphadenopathy
6. B symptoms or paraneoplastic phenomena, which, in the opinion of the
investigator are the result of progressive WM.
- Life expectancy >12 months
- ECOG < 3
- Able to provide informed consent
- Ability to understand the requirements of the study, provide written informed
consent, including consent for the use and disclosure of research-related health
information, and comply with the protocol procedures, including required study
- Subjects of child bearing potential must agree to use effective contraception
throughout the study and for 3 months after the last dose of belimumab
- Prior therapy with belimumab.
- Pregnant or breast feeding
- Chemotherapy, immunotherapy or biological therapy within 4 weeks of enrolment.
Therapeutic plasma exchange can continue- see section 3.1.4.
- Creatinine clearance (calculated by Cockcroft-Gault) < 60ml/min
- Bilirubin >2x ULN, ALT >2x ULN.
- History of an allergic or anaphylactic reaction to parenteral administration of
contrast agents, human or murine proteins or monoclonal antibodies, a history of
severe allergic reaction to drugs, food, or insects requiring medical intervention,
or a history of hypersensitive triad (having all 3 features of allergic rhinitis with
nasal polyps, asthma, and aspirin sensitivity).
- Prior opportunistic infection including tuberculosis or atypical mycobacterial
infection, multi-dermatome Herpes Zoster or Pneumocystis pneumonia or invasive fungal
infection (not including oral or vaginal candidiasis or superficial dermatophytes) .
- Active infection with hepatitis B, hepatitis C or HIV or historically positive test
or test positive at screening for HIV antibody, hepatitis B surface antigen, or
hepatitis C antibody.
- History of organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem
- Planned surgical procedure during the treatment period of this study or a history of
any other medical disease (eg, cardiopulmonary), laboratory abnormality, or condition
that, in the opinion of the principal investigator, makes the subject unsuitable for
- Hospitalization for treatment of infection within 60 days of Day 1.
- Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals,
or anti parasitic agents) within 60 days of Day 1.
- Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or
dependence within 364 days prior to Day 1.